A functional genetic screen identifies Aurora kinase b as a critical regulator of Sox9-positive embryonic lung progenitor cells
Journal Title
Development
Publication Type
epub ahead of print
Abstract
Development of a branching tree in the embryonic lung is critical for the formation of a fully mature functional lung at birth. Sox9+ cells present at the tip of the primary embryonic lung endoderm are multipotent cells responsible for branch formation and elongation. We performed a genetic screen and identified Aurora kinase b (Aurkb) as a critical regulator of Sox9+ cells ex vivo. In vivo conditional knockout studies confirmed that Aurkb was critical for lung development but was not necessary for postnatal growth and the repair of the adult lung after injury. Deletion of Aurkb in embryonic Sox9+ cells led to the formation of a stunted lung that retained the expression of Sox2 in the proximal airways, as well as Sox9 in the distal tips. While we found no change in cell polarity, we showed that loss of Aurkb or chemical inhibition of Aurkb induced a block of Sox9+ cells in G2/M, likely responsible for the lack of branch bifurcation. This work demonstrates the power of genetic screens in identifying novel regulators of Sox9+ progenitor cells and lung branching morphogenesis.
Publisher
Company of BIologists
Keywords
Aurora kinase b; Genetic screen; Lung development; Sox9
WEHI Research Division(s)
Personalised Oncology; Advanced Technology And Biology; Epigenetics And Development
PubMed ID
34121118
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-06-21 10:25:54
Last Modified: 2021-06-21 10:30:10
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